1. Field of the Invention
The application relates to the field of neurobiology. In particular, the application relates to agents, compositions and methods useful for neuroprotection, specifically, for preventing, slowing the progression or onset of, or reducing the risks of a central nervous system disease in a patient, particularly a demyelinating disease.
2. Description of Related Art
Alzheimer's disease (AD) is a neurodegenerative disease of the central nervous system (CNS) that usually affects people over 65 years old. Although typically presenting with symptoms in the aged, the disease can develop many years before it is diagnosed. When symptoms first appear, the patients often exhibit memory loss and, at later stages, confusion, anger, mood swings, language difficulties, long-term memory loss and a sense of withdrawal. As the disease progresses, minor and major bodily functions are lost, leading ultimately to death. The disease is associated with amyloid plaque deposits and tangles in the brain, but the cause of AD is not well understood. Currently, there is no effective treatment to stop or cure AD. Thus, a better way to prevent and manage the disease is essential.
Parkinson's disease (PD) is another neurodegenerative disorder of the CNS. PD is characterized by muscle rigidity, tremor, a slowing of physical movement, and, in severe cases, a total loss of movement. The primary symptoms of PD are caused by decreased stimulation of the motor cortex by the basal ganglia, usually a result of insufficient production and activity of dopamine produced by the dopaminergic neurons of the brain. In addition to its effects on motor function, PD is also associated with non-motor symptoms such as disorders of mood, behavior, thinking and sensations. Most PD patients are characterized as having idiopathic Parkinson's disease, i.e., having no specific identified cause. Less commonly, PD is associated with genetic lesions, toxins, head trauma, and can be drug-induced. PD is a chronic disorder that requires long-term management and care for patients. Currently, there is no cure for PD, but medication and surgery can provide temporary relief of the symptoms. Although PD is not considered a fatal disease, it may cause complications in its late stages such as choking, pneumonia and falls and can lead to death.
Multiple sclerosis (MS) is an autoimmune disease in which the immune system attacks the CNS, leading to demyelination. MS patients often suffer from a variety of symptoms, including changes in sensation, difficulties in moving, problems in speech and vision, fatigue, and acute or chronic pain. In MS patients, the immune system attacks oligodendrocytes, destroying the myelin sheath and affecting neural signal transmission in the white matter of the CNS. MS patients may suffer from relapsing forms or progressive forms of symptoms. In patients experiencing relapses, symptoms may disappear completely between episodes, but permanent neurological problems persist, especially as the disease advances. Although the cause of MS is not well understood, environmental factors can play a role, and genetic factors may determine the susceptibility of an individual to MS. Like the other neurodegenerative diseases AD and PD, currently there is no cure for MS.
In addition to MS, there are a number of other demyelinating diseases that are characterized by damage to myelin in the CNS. There are at least two types of demyelinating diseases, acquired and hereditary neurodegenerative disorders. The causes of these diseases are different, but the outcome is the same: loss of vision, hearing, ability to walk or speak and other life-altering changes. Further, dysmyelinating diseases (where myelin sheath is present but defective) may show similar symptoms. Because of the multi-faceted etymologies of diseases resulting from damaged or non-functional myelin in the CNS, they are difficult to diagnose and often impossible to cure.
Because these chronic neurodegenerative diseases are refractory to treatment, neuroprotection is an important component of disease management. For example, ibuprofen is a widely used non-steroid anti-inflammatory drug (NSAID) for relief of a variety of inflammatory symptoms. Ibuprofen has been used as a treatment of AD; however, the gastrointestinal side-effects associated with Ibuprofen has limited its suitability for daily administration to patients with neurodegenerative disease. Thus, there exists a need for better and more effective treatments resulting in neuroprotection in patients suffering from or susceptible to neurodegenerative diseases.